title: Novel mouse model of combined hyperlipidemia associated with steatosis and liver injury by a single-dose intragastric administration of schisandrin B/cholesterol/bile salts mixture.
abstract: Hyperlipidemia is referred to as hypercholesterolemia, hypertriglyceridemia, or both in combined hyperlipidemia. Here, a novel mouse model of combined hyperlipidemia is described. Mice were orally given a single dose of a modeling agent (MA) made of a mixture of schisandrin B/cholesterol/bile salts (1/2/0.5 g/kg) suspended in olive oil. MA treatment increased serum triglycerides (TG) and total cholesterol (TC) (up to 422% and 100% at 12 - 96 h post-treatment, respectively) and hepatic TG and TC (up to 220% and 26%, respectively) in a time- and dose-dependent manner, associated with elevation of high-density lipoprotein and low-density lipoprotein levels. Serum alanine/aspartate aminotransferase activities, indicators of liver cell damage, were also elevated (up to 198%) at 48 and 72 h post-MA treatment. Fenofibrate blocks MA-induced hyperlipidemia, lipid accumulation in the liver, as well as liver injury. Oral administration of a mixture of schisandrin B, cholesterol, and bile salt could generate an interesting mouse model of combined hyperlipidemia associated with hepatic steatosis and steatohepatitis.
authors.affiliation: Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Pan
authors.forename: Zhan-Hong
authors.initials: ZH
authors.lastname: Jia
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.forename: Pei-Li
authors.initials: PL
authors.lastname: Zhu
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
authors.forename: Kam-Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control; D002784:Cholesterol / Q000008:administration & dosage / Q000009:adverse effects; D034242:Cyclooctanes / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced / Q000517:prevention & control; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D017705:Lignans / Q000008:administration & dosage / Q000009:adverse effects; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D034242:Cyclooctanes; D017705:Lignans; D008074:Lipoproteins; D011083:Polycyclic Compounds; D014280:Triglycerides; C015499:schizandrin B; D002784:Cholesterol; D011345:Fenofibrate